Diffuse Large Cell LymphomaPhase 2NCT00144807
ACVBP Plus Rituximab in Patients Aged From 18 to 59 Years With High-risk Diffuse Large B-cell Lymphoma
A Phase 2 study testing rituximab, doxorubicin and cyclophosphamide in people with Diffuse Large Cell Lymphoma, run by Lymphoma Study Association at 13 sites in 3 countries.
Trial summary
This study is a multicentric trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Diffuse Large Cell Lymphoma
- What is being tested?
- rituximab, doxorubicin and cyclophosphamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 13 sitesin 3 countries
- Study dates
- Dec 2003to Apr 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification).
- Age from 18 to 59 years, eligible for transplant. Patient not previously treated. Age adjusted IPI = 2 or 3 With a minimum life expectancy of 3 months Negative HIV, HBV and HCV serologies < 4 weeks (except after vaccination). Having signed a written informed consent.
Who cannot join
- Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.
- Central nervous system or meningeal involvement by lymphoma. Contra-indication to any drug contained in the chemotherapy regimens. Poor renal function (creatinin level >150 mmol/l), poor hepatic function (total bilirubin level >30 mmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
- Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration.
- Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.
- Any serious active disease (according to the investigator's decision). Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.
- Pregnant or lactating women Adult patient under tutelage.
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
France11 sites
Polyclinique Bordeaux Nord
Bordeaux, 33300
Hôpital Henri Mondor
Créteil, 94010
Hématologie CHU de Lille
Lille, 59000
Centre Léon Bérard
Lyon, 69008
Hôpital Saint Louis
Paris, 75010
Hématologie Adultes - Hôpital Necker
Paris, 75743
Service d'Hématologie - Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69495
Centre Hospitalier Robert Debré
Reims, 51092
Centre Henri Becquerel
Rouen, 76038
Hématologie CHU Purpan
Toulouse, 31059
Institut Gustave Roussy
Villejuif
Switzerland1 site
Schweirische Arbeitsgruppe fur klinische Krebsforschung
Lausanne
About this study
Official title: Study of ACVBP Plus Rituximab in Previously Untreated Patients Aged From 18 to 59 Years With High Risk Diffuse Large B-cell Lymphoma (Age-adjusted IPI = 2-3)
This study is a multicentric trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma
Read the detailed description
This phase II non randomized study is based on the results of the LNH 98-5, LNH 87-2, LNH 93-3 and LNH 98-3B studies.
To date, the ACVBP regimen is considered as the reference induction treatment of the GELA in patients with 2-3 adverse prognostic factors. Indeed neither NCVBP regimen (LNH87-2) nor ECVBP (LNH93-3) led to increase the complete remission rate. More recently, the addition of etoposide to doxorubicin and cyclophosphamide (LNH98-3B) did not enhanced the complete remission rate with more toxicity. In patients < 60 years with 2-3 adverse prognostic factors the complete remission rate remained less than 65% in all these studies. Consequently, increasing the quality of response remains a major goal in this group of young patients with adverse prognostic factors.
It has been shown that the addition of rituximab to CHOP regimen significantly improved the CR rate in elderly patients with previously untreated large B-cell lymphoma when compared with CHOP alone without additional toxicities. Moreover, event-free survival and overall survival were found to be longer in the R-CHOP group. The present trial will evaluate the response rate obtained after four cycles of ACVBP combined to rituximab (R-ACVBP) before high dose therapy consolidative treatment in this group of higher risk patients.
The LNH87-2 study has shown that intensive consolidation treatment with autologous stem cell support was beneficial to high risk patients in good response after a full induction phase. The long-term results of this randomised study prompted us to consider high dose therapy as the best consolidative option for these patients.
- Conditions
- Diffuse Large Cell Lymphoma
- Being tested
- rituximab, doxorubicin, cyclophosphamide, autologous stem cell transplantation
- Keywords
- lymphoma, diffuse large B-cell, rituximab, chemotherapy, autologous stem cell transplant
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
doxorubicinDrug
cyclophosphamideDrug
autologous stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| R-AC | Experimental | rituximab + doxorubicin + cyclophosphamide + autologous stem cell transplantation Receives: Drug: rituximab; Drug: doxorubicin; Drug: cyclophosphamide; Procedure: autologous stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission rate (CR + CRu)
4 cycles of ACVBP
Measured: 12 weeks
Secondary outcomes (1)
Event-free survival and overall survival of patients submitted to autologous transplant and of the entire study population
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startDec 2003
- Primary completionSep 2008
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lymphoma Study Association
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier Fitoussi, MD, Principal investigator, Lymphoma Study AssociationChristian Gisselbrecht, MD, Study director, Lymphoma Study AssociationCorinne Haioun, MD, Study chair, Lymphoma Study AssociationHervé Tilly, MD, Study chair, Lymphoma Study Association
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00144807
- Sponsor's protocol ID
- LNH03-3B
- Status last verified
- Sep 2015
- First submitted
- 2 Sep 2005
- Last updated
- 2 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.
PubMed 15867204Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Briere J, Gaulard P, Reyes F. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol. 2000 Aug;18(16):3025-30. doi: 10.1200/JCO.2000.18.16.3025.
PubMed 10944137Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. doi: 10.1182/blood-2003-02-0542. Epub 2003 Aug 14.
PubMed 12920037Ghesquieres H, Larrabee BR, Haioun C, Link BK, Verney A, Slager SL, Ketterer N, Ansell SM, Delarue R, Maurer MJ, Fitoussi O, Habermann TM, Peyrade F, Dogan A, Molina TJ, Novak AJ, Tilly H, Cerhan JR, Salles G. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol Oncol. 2017 Dec;35(4):447-455. doi: 10.1002/hon.2305. Epub 2016 Jun 10.
PubMed 27282998Copie-Bergman C, Cuilliere-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, Recher C, Petrella T, Ketterer N, Peyrade F, Haioun C, Nagel I, Siebert R, Jardin F, Leroy K, Jais JP, Tilly H, Molina TJ, Gaulard P. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015 Nov 26;126(22):2466-74. doi: 10.1182/blood-2015-05-647602. Epub 2015 Sep 15.
PubMed 26373676Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G, Feugier P, Ferme C, Ysebaert L, Gabarre J, Herbrecht R, Janvier M, Van Den Neste E, Morschhauser F, Casasnovas O, Ghesquieres H, Anglaret B, Brechignac S, Haioun C, Gisselbrecht C. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011 Aug;96(8):1136-43. doi: 10.3324/haematol.2010.038109. Epub 2011 May 5.
PubMed 21546499
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of ACVBP Plus Rituximab in Previously Untreated Patients Aged From 18 to 59 Years With High Risk Diffuse Large B-cell Lymphoma (Age-adjusted IPI = 2-3)
- ClinicalTrials.gov ID
- NCT00144807
- Acronym / sponsor ID
- LNH03-3B
- Conditions
- Diffuse Large Cell Lymphoma
- Keywords
- lymphoma, diffuse large B-cell, rituximab, chemotherapy, autologous stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Lymphoma Study AssociationUniversity, hospital or other
- Study start
- Dec 2003
- Primary completion
- Sep 2008 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 5 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicentric trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma
Detailed description
This phase II non randomized study is based on the results of the LNH 98-5, LNH 87-2, LNH 93-3 and LNH 98-3B studies.
To date, the ACVBP regimen is considered as the reference induction treatment of the GELA in patients with 2-3 adverse prognostic factors. Indeed neither NCVBP regimen (LNH87-2) nor ECVBP (LNH93-3) led to increase the complete remission rate. More recently, the addition of etoposide to doxorubicin and cyclophosphamide (LNH98-3B) did not enhanced the complete remission rate with more toxicity. In patients < 60 years with 2-3 adverse prognostic factors the complete remission rate remained less than 65% in all these studies. Consequently, increasing the quality of response remains a major goal in this group of young patients with adverse prognostic factors.
It has been shown that the addition of rituximab to CHOP regimen significantly improved the CR rate in elderly patients with previously untreated large B-cell lymphoma when compared with CHOP alone without additional toxicities. Moreover, event-free survival and overall survival were found to be longer in the R-CHOP group. The present trial will evaluate the response rate obtained after four cycles of ACVBP combined to rituximab (R-ACVBP) before high dose therapy consolidative treatment in this group of higher risk patients.
The LNH87-2 study has shown that intensive consolidation treatment with autologous stem cell support was beneficial to high risk patients in good response after a full induction phase. The long-term results of this randomised study prompted us to consider high dose therapy as the best consolidative option for these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-AC | Experimental | Drug: rituximab, Drug: doxorubicin, Drug: cyclophosphamide, Procedure: autologous stem cell transplantationrituximab + doxorubicin + cyclophosphamide + autologous stem cell transplantation |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification).
- Age from 18 to 59 years, eligible for transplant. Patient not previously treated. Age adjusted IPI = 2 or 3 With a minimum life expectancy of 3 months Negative HIV, HBV and HCV serologies < 4 weeks (except after vaccination). Having signed a written informed consent.
Key exclusion criteria (6 listed)
- Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.
- Central nervous system or meningeal involvement by lymphoma. Contra-indication to any drug contained in the chemotherapy regimens. Poor renal function (creatinin level >150 mmol/l), poor hepatic function (total bilirubin level >30 mmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
- Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration.
- Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.
- Any serious active disease (according to the investigator's decision). Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximab | Drug | R-AC |
| doxorubicin | Drug | R-AC |
| cyclophosphamide | Drug | R-AC |
| autologous stem cell transplantation | Procedure or surgery | R-AC |
Primary outcome
Complete remission rate (CR + CRu)
Time frame: 12 weeks
4 cycles of ACVBP
1 secondary outcome
Event-free survival and overall survival of patients submitted to autologous transplant and of the entire study population
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2015.
- Background: PubMed 15867204Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.
- Background: PubMed 10944137Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Briere J, Gaulard P, Reyes F. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol. 2000 Aug;18(16):3025-30. doi: 10.1200/JCO.2000.18.16.3025.
- Background: PubMed 12920037Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. doi: 10.1182/blood-2003-02-0542. Epub 2003 Aug 14.
- Derived from this study: PubMed 27282998Ghesquieres H, Larrabee BR, Haioun C, Link BK, Verney A, Slager SL, Ketterer N, Ansell SM, Delarue R, Maurer MJ, Fitoussi O, Habermann TM, Peyrade F, Dogan A, Molina TJ, Novak AJ, Tilly H, Cerhan JR, Salles G. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol Oncol. 2017 Dec;35(4):447-455. doi: 10.1002/hon.2305. Epub 2016 Jun 10.
- Derived from this study: PubMed 26373676Copie-Bergman C, Cuilliere-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, Recher C, Petrella T, Ketterer N, Peyrade F, Haioun C, Nagel I, Siebert R, Jardin F, Leroy K, Jais JP, Tilly H, Molina TJ, Gaulard P. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015 Nov 26;126(22):2466-74. doi: 10.1182/blood-2015-05-647602. Epub 2015 Sep 15.
- Derived from this study: PubMed 21546499Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G, Feugier P, Ferme C, Ysebaert L, Gabarre J, Herbrecht R, Janvier M, Van Den Neste E, Morschhauser F, Casasnovas O, Ghesquieres H, Anglaret B, Brechignac S, Haioun C, Gisselbrecht C. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011 Aug;96(8):1136-43. doi: 10.3324/haematol.2010.038109. Epub 2011 May 5.
- Official site of the Groupe d'Etudes des Lymphomes de l'Adulte (In french)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Fitoussi, MD principal investigator
Lymphoma Study Association
Christian Gisselbrecht, MD study director
Lymphoma Study Association
Corinne Haioun, MD study chair
Lymphoma Study Association
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab, doxorubicin and cyclophosphamide in people with Diffuse Large Cell Lymphoma, run by Lymphoma Study Association at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, Belgium, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission rate (CR + CRu) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00144807, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2015.